 I'd like to introduce Dr. Michael Ruscio, who will speak about the gut microbiota in health and disease research and recommendations. Thank you. Well, hi, everyone. Thank you for coming. Everyone can hear me okay? Okay. So, my name is Michael Ruscio. I am an alternative physician here in Wallet Creek, and gastrointestinal problems are a major part of my practice. And they were a major part of my own kind of career. I was on par to go into conventional medicine, and then I ended up acquiring a amoebic infection, really kind of opened my eyes to how important the gut was, and I shifted gears into alternative medicine. And so now, pretty much every patient I see, we have some kind of gut work that we have to do. And I've been really following the microbiota research to see if we can extract any kind of clinical pearls from that. So we'll jump right in. There's a lot of stuff that I want to cover. We'll talk about what is the gut microbiota, why is it important? We'll look at a comparison of different microbiotas, modern versus ancestral, and also westernized versus developing areas. We'll look at the microbiota in disease, IBD, obesity and autoimmunity. And we'll also look at manipulating the microbiota with diets, probiotics, prebiotics, fiber, and antimicrobials. There are other things here that we can potentially put in, like fecal transplant and helmetic therapy, but those aren't really accessible to many people. So I'm just going to focus on the things that you have more readily available to you, and then we'll wrap up with a few conclusions. So to quote, the gut microbiota has co-evolved with humans and can be considered an organ of similar size as the liver. And the relationship between the microbiota and the host is one of the most ancient stories of co-evolution. In fact, as we look at different populations, we see different bacteria that shift in order for that population to survive. One of the things that we can't do as humans is evolve our genes very quickly. So if the environment changes rapidly, we're in trouble because we can't always change our DNA and our genes to keep pace with that. But we can borrow from bacteria that have the ability to very rapidly evolve their DNA through what's known as horizontal gene transfer. So one of the things that's happened is as the environment changed quickly and we haven't necessarily been able to change our genes to keep up, we've borrowed the fast, adaptable genes of bacteria to allow us to keep pace with the changing environment. Okay, so what is a microbiota? Why is it important? Well, it does a number of things for us. Roughly 10% of our calories are from bacterial fermentation, production of B vitamins and K vitamins, like we just discussed, enables us to survive and adapt faster using bacterial genes. And we also see the production of short-chain fatty acids, which are reparative to the intestinal cells. We also see toning of the immune system and the ability to crowd out pathogens from being able to infect the GI tract. Detoxification, breakdown and removal of various toxins is also assisted by the gut microbiota and also a partial regulation of metabolism. So when you read some of the literature, it can be very confusing. Sometimes they talk in phyla, sometimes they talk in genus, sometimes they talk in species. So I just want to give a quick overview to help orient you to some of the nomenclature. So the domain is prokaryotes, kingdom of course bacteria. But there's also some fungus. People have probably heard of Candida infections and yeast and things like that. There's also Archaea. Now Archaea, the most well-known is methanobreverbacter smithii, which is the organism that can cause constipative small intestinal bacterial overgrowth. It's a form of organism that secretes methane, methane gas, and you'll see this on testing for people that have small intestinal bacterial overgrowth. And also interestingly viruses play a role in the gut. Now what bacteria will do is they will use viruses to exert antibacterial effect over some of their other bacterial competitors through what's known as phage function. So viruses are also there. They're a small percent, but viruses also play a role in the microbiota. Now at the phylum level, there's about nine well-established phylum, one of which is just an example is Formicides. This is where we currently have the best level of understanding. We go deeper into class, family, genus, like lactobacillus, and then species, lactobacillus acidophilus, of which there's about a thousand. We usually speak in terms of lactobacillus acidophilus, bifidobacterium, and phantase. This is what we're typically used to speaking about. But the literature, we see much more of an understanding here, sometimes with species mixed in, because we just haven't gotten good enough to get that deeper level of understanding down to the species level yet. So when we look at the phylum level, we see Formicides is usually the major player in pretty much every society that we see, and in most mammals in general. Bacteroides is usually second to that, and then actinobacteria and proteobacteria represent more of a minority. These links you're seeing here are just to the PubMed abstracts if you wanted to pull the papers on these. So now let's get into comparison of different microbiota. So I want to give you some of this section. Increased diversity seen with decreased hygiene. So let's talk about that briefly. So in this study, you're looking at the number of operational taxonomical units. This is just a measure of diversity. So the more of that you see, the more diverse bacteria you have, which is good. That's what you want. Diversity is good. So you see the US pales a comparison to these other two non-industrialized, non-highly hygienic societies, the Amerindians and Malawians. So you see when we compare to more third world type countries, they have much more bacterial diversity in their microbiota. Again the same thing represented in another study where they compared the gut of children from the United States to those of Bangladesh. And we see here both a phylum level comparison and a species level comparison. Bangladesh are the empty circles US or the solid circles and you see again far more diversity in the Bangladesh children. So the dirtier the environment, the more diverse the colonization. So now number two, novel even pathogenic bacteria may be present in certain areas to a with digestion of unique foodstuffs. So if we look at the Hadza. The Hadza are maybe the last group of untouched hunter-gatherers and this is the area that they habitat. They have 70% of their diet comes from plant foods, highly fibrous tubers, honey and berries, 30% from birds and game animals. Now what do we see in the Hadza and here's a reference for this paper here. We see increased treponema which is considered an opportunistic infection in industrialized countries. It's a spirochipacterium which can cause syphilis but it's proficient at breakdown of xylein and cellulose. So interestingly this infection is actually symbiotic for the Hadza. They also have higher levels of that bacterioidates and a lower level of formicates with enrichment and prevotella. This will be more important when we discuss the implications of the microbiota to obesity because in obesity it's often said that if you have high bacterioidates and low formicates that's protective against obesity. And we see some studies like this where that conclusion is being drawn from but I'll show you evidence later that contradicts that and it's not really that simple. And maybe the most shockingly they have no bifidobacterium. Bifidobacterium is one of the most well studied and one of the most clinically efficacious strains that we have in Westernized societies and studies in, for example, IBS have shown a decreased diversity in count of bifidobacteria in patients with IBS. So we know that in Western societies bifidobacteria is good. You've probably all heard of some kind of bifidobacterium supplement, right? But there's none of that in the Hadza. And the Hadza have very, very healthy GI tracts, generally there's an excellent health. It's been hypothesized that meat and dairy or livestock contact may be needed for bifidobacterium colonization and maintenance. So what we see here is very interesting, right? We see a very healthy group of hunter-gatherers yet they have none of what we would consider good, the bifidobacterium, and they have what may be considered an infection by United States standards that's actually playing a symbiotic role for them. You guys with me on this so far? Okay. Okay, so now we'll look at increase in carbohydrate-digesting microbiota in populations with higher carbohydrate intake. And this is what I think is maybe one of the most interesting parts of this presentation. So going back to the Hadza paper, what you're seeing here and you probably can't see this, but this is a graph and the darker the color, the higher the density of that particular bacteria, okay? So here we're looking at Italians and people from the United States. So they have a high representation here. Now here we're looking at just Italians. So this is all westernized, okay? Moving over here to other columns here and here, this is Burkina Faso or Africans against the Malawians, okay? So two agrarian societies that are non-industrialized. They're farmers, they're non-industrialized, they're somewhat third world. So we see a very different representation here. Now compare that to the Hadza. They have a completely different enrichment in their bacteria. So what we see is from society to society to society, from westernized to agrarian to hunter-gatherer, we see different parts of the bacterial spectrum have increased or decreased densities. So what does that mean? Well, when we look at this next paper, I'm sure some of you have probably heard of the paper comparing the Africans to the Italians, okay? When we look at the paper looking at the Africans to the Italians, and again, these are native Africans, we see here, you see this blue outline? This is the bacterioidates. So they have a lot of bacterioidates, and the red here is formicides, and they have a lot less. Compared to the Italians, which are more westernized, have much more of this formicides and much less of this bacterioidates. This is part of where the hypothesis comes from that high bacterioidates is protective against obesity. But there may be more to it than that. So part of what we see here in this bacterioidates is that prevetella is a major constituent here. And prevetella is needed to break down carbohydrate, possibly to break down grain. So we know that the Birkenfaso have a high consumption of carbohydrate, high consumption of grain, a high representation of this prevetella. But when we look at other populations that are similar, like the Russian population that has a similar diet, high in grain, high in carbs, high in potatoes, they don't experience this enrichment in prevetella or this increase in bacterioidates. And more importantly, when we look at paleofecal samples, we do not see the same shifts of increased bacterioidates, okay? So this is a fantastic paper. They actually got samples from two people who lived in the paleolithic era. And what do you see here? Bacterioidates is fairly underrepresented compared to the Africans, right? So here's the Africans. This is the bacterioidates here, this blue bar on the outside. So major constituent to the Africans. But in the paleofecal samples, we don't see that same enrichment. So what does this tell us? Well, we can draw some inferences from this. It may mean that the people in the paleolithic era did not eat the same high level of carbohydrates that we see in modern day Italians, okay? That's the inference I draw from this. We also see from one sample to the other. These are two different people, Z1 and Z2, two different people. We see that the fermicides, which is the purple part here, shifts greatly. Now, we don't know why that is. What's been shown in the Hadza though, is that because the women do more foraging and the men do more hunting, there's actually a sex difference in the representation of the microbiota. The women have more of that treponema to help break down more of this island and cellulose because they're doing more foraging and snacking while they eat, they need more of that. Men are doing more hunting, eating more meat. So this may be a sex differentiation we're seeing here. But to zoom out, the conclusion I'm trying to draw from this comparative analysis is oftentimes when we study third world countries, they are dirtier and they have more diverse colonization, which is generally good, right? But they also don't have as much money so they eat cheap food, right? Lots of carbs and grains and things like that. So sometimes the conclusion that's made is, well, they're healthy, they eat lots of carbs, we should eat lots of carbs too. And I'm not saying that's wrong, but I think there's some flawed assumptions being made within that paradigm, okay? Because it may be that the people in the third world countries derive most of their health because they grow up and live in a dirty environment, which has continuously been shown to be very good for your immune system. And for your gut. And they may be able to survive well and be healthy on whatever diet they eat because they have this healthy microbiota and this healthy immune system and this healthy gut. Hopefully I didn't lose anybody with that. Okay, so moving on, modern dirt, bad old dirt good. Coming back to the comparison of US to Bangladesh, what we see is that the children in Bangladesh that grew up in more slum-like conditions, yes, they had much more diversity. But they also had a high incidence of diarrheal diseases. But the Hadza that were also diverse but grew up in a more hunter-gatherer society again had the high diversity but did not have the diarrheal diseases. So what this may mean is old dirt, good, modern dirt, bad, right? And I think that makes sense. We evolved in an old dirt scenario. We did not evolve in a modern day dirty scenario. So it's a key differentiation I think that needs to be made because sometimes people hear that dirt is good for you and then they throw hygiene out the window. And it may not be that simple. It's the type of hygiene may be what's important. So looking at the microbiota now in IBD or inflammatory bowel disease published in the journal Gut, we see here for mykides again. And the white line is the diversity of healthy people and the black line is the diversity of people with Crohn's disease. So you can clearly see people with Crohn's disease have far less diversity. And the authors concluded we see a reduced complexity of the bacterial phylum for mykides in patients with Crohn's disease. So again, reduced or decreased diversity is really a problematic issue. And again, we see from the Journal of Inflammatory Bowel Disease representation of ulcerative colitis compared to healthy people compared to Crohn's disease. And we just see different representations in the predominant bacteria in these three different populations. But again, ulcerative colitis and Crohn's far different than healthy. And from nutrition reviews, we see that Crohn's, one of the things we see in Crohn's is getting down to the species level is reduced fecal bacteria and prosnitsi and then ulcerative colitis. We see decreased amucinophilia. Not a whole lot we can do with that just yet, but there's just observations that we're starting to piece together nonetheless. But where we do have some good interventions for inflammatory bowel disease is with anti-inflammatory agents. And these may work very well because it's not a one way street from the microbiota to the immune system. It's a bi-directional relationship. Meaning that the microbiota, I'm sorry, the immune system shapes the microbiota and the microbiota shapes the immune system. What happens in inflammatory bowel disease, IBD, is people's immune systems are overzealous and they start killing and pruning the healthy commensal bacteria. Okay, so that's why the anti-inflammatories seem to work well because you're toning down that overzealous immune response. Okay, now the microbiota and obesity, there's so much information I've gone through. I'm just going to kind of give you the executive level summary here. The fermicities of the bacteria to tease ratio, okay? This is something that you'll maybe hear a lot about. When you go into the medical literature, you see the animal model hypothesis definitely supports an alteration, a high fermicities sub-bacteriorities ratio correlated with obesity. When you go into the human level studies, there are several contradictions. So that hypothesis does not hold its own weight in human studies. So we can't really apply that to humans. But in healthy versus obese microbiota, again, there's no consistent difference, but there is consistently a difference. Okay, so consistently obese are different than healthy. It's just that difference is not consistent with except maybe the one exception of decreased diversity which seems to be the reoccurring theme here that decreased diversity is kind of the kiss of death when it comes to your microbiota. Now, short chain fatty acids is another contentious issue regarding obesity. Again, short chain fatty acids are just carbohydrate foodstuffs that we can't digest. The bacteria digest for us and they secrete short chain fatty acids which give us some energy and which also are very reparative to the intestinal cells. So one of those is butyrate and butyrate levels have been consistently shown to be elevated in the obese. So it's somewhat paradoxical because butyrate is supposed to be so healthy for the colon, yet people who are obese have high levels of butyrate. Now, the high levels of butyrate may be because people who are obese are eating lots of carbohydrates or more food in general and supplying more substrate to produce these short chain fatty acids. But also may be that people who are obese have an increased ability to harvest energy from food. You've probably heard something along these lines before and here's maybe a support for that. The Hadza also had high short chain fatty acids but they had high propionate. Now, this is my hypothesis as to what's happening here. The Hadza don't have as much food, they live in a much more harsh environment. So for them to be able to extract as much calories from their food as possible would be a survival advantage, right? So they make a lot of short chain fatty acids are very good at extracting all the calories they can from food, but put them in a Westernized society where there's plenty of food and they are extracting a ton of energy from it, they may be more prone to become obese. So the high ability to extract short chain fatty acids from foods may be an adaptation to help you survive through famine, but when you put that into a modernized society it may become problematic. The other interesting thing about short chain fatty acids is low carb diets will decrease short chain fatty acids which is one of the criticisms of low carbohydrate diets in the long term because you may do damage to your healthy bacteria and you may do damage to your colon because you starve it of the short chain fatty acids that are needed to repair the colon. However, paradoxically, they're also very effective for weight loss and paradoxically even further yet still some interventions with things like prebiotics and fiber that increase short chain fatty acids have shown a modest ability to decrease weight. So the picture of short chain fatty acids and obesity is not incredibly clear at this point. What is a little bit more clear is inflammation. I'm sure some of you have heard that people who are obese tend to have more inflammation in the gut, more of what's called endotoxemia or more of these LPS lipopolysaccharides. Now, what may be happening in people that are obese is they don't have a lot of exposure to a lot of diverse exposure to bacteria early in life and when they don't, their immune system tends to be more inflammatory. So they eat, that stimulates inflammation and then inflammation can cause insulin resistance and can cause a slowing of metabolism. So what may happen in obese is the obese, the obese may have poor colonization, that poor colonization causes them to be more inflammatory and then inflammation sets the stage for metabolic derangement. Now, one of the ways that we can guard against that is early diverse exposure to bacteria, which is kind of a segue into the next section, which is microbiota and autoimmunity, okay? So in the Journal of Allergy and Clinical Immunology, what they're showing here, again, this is diversity, okay? So the higher you go, the more diverse and this is age. Now, in children that only achieve a minor amount of diversity, they are more prone to become allergic later in life and what typically happens is this, you have a window and once you pass this window, maybe about two or three years of age, you don't really gain any more diversity. So you can't really gain much diversity after three, okay? So you hit three, the diversity you have, you're kind of locked in with and give that a few years and that can become allergies and asthma compared to the people that hit this higher level of diversity, give that a few years and they become healthy, okay, and this has been supported by numerous studies, another one of which is here. This is looking at pre-animal farm exposure and it's a relationship to allergy and immunity. What you're seeing here is a number of different farm animal species that mother had contact with during pregnancy, okay? So the farther we go to the right, the more animals, okay? Zero to six, zero to six, zero to six and what you're seeing here are receptors for the immune system, tolic receptor, two, four and CD14 cells. The more of these you have, the more trained your immune system is to be able to distinguish self from non-self, which is one of the fundamental tenants of autoimmunity, okay? When your immune system doesn't have good aim, it's not sure, is that a thyroid or is that a bacteria? Okay, and it just starts shooting whatever, starts shooting your thyroid tissue, now you have Hashimoto's. So the more of these tolic receptors you have, the better the immune system is at distinguishing self to non-self, okay? And so what you see here is the more animals mom is exposed to, the more of these receptors are expressed. What ends up happening is these become protective factors. So farm milk consumption, regular contact with animals, frequent stable or barn visits for hanging and especially maternal stable work during pregnancy causes a very profound effect on allergies and asthma. The earlier and the more diverse the exposure, the better. So essentially again, what this is saying is the more dirty mom got, the healthier the child was in terms of allergies and asthma because we had increased expression of these receptor cells that help the immune system say, you're a piece of good tissue, I'm not going to destroy you, you're a bad guy, I'm going to attack you, which is the fundamental confusion that happens in autoimmunity. You guys with me on that? Yeah, okay. Now, backing up for one second here, that has implications potentially for obesity because if these receptors are working well and the immune system is working well, you become less inflamed. And if inflammation can feed obesity, then we know that whatever we can do to stop inflammation will potentially help prevent obesity. So early exposure, like we're showing here, can help with allergies and asthma as verified in the peer-reviewed literature and there's some evidence showing that it may also help with obesity. So this then leads to the question of parasites, friends or foe, okay? Because I spend a lot of time treating patients for infections, yet a lot of this information would make you think you want to have as many infections as in bacteria as possible because it's very good for you. I'm sure many of you have seen this before. This is published in the New England Journal of Medicine showing as infectious diseases are going down, allergic and autoimmune diseases are going up. This is what we see in many Westernized countries as we have less exposure to dirt and germs, we have less infectious disease, but because with that you're becoming so much more sterile, that sort of cripples your immune system and now you're more prone to have allergic and autoimmune conditions. So you sacrifice one for the other. And certainly we see other data points that support this. To quote, these results suggest a protective benefit of ACE pylori infection against the development of inflammatory bowel disease. So the more ACE pylori infections there were in this study, the less inflammatory bowel disease. Because ACE pylori may be a proxy for a dirty environment. But here's where these things get a little bit mucky. Another study, 10 patients that had Hashimoto's which is thyroid autoimmunity and an ACE pylori infection were studied. Half were then treated for ACE pylori, the other half were not. Those treated for ACE pylori saw a marked and significant decrease in their thyroid autoimmunity. So how do we account for this? How can ACE pylori be protective against some autoimmune conditions but trigger potentially other autoimmune conditions? Well, I think it has to do with timing one in context two. So timing, if these inoculations occur before three years of age and before the gut stabilization window closes at about three years of age, they tend to be protective. So beneficial before three years of age but later in life they can potentially be detrimental. This, by the way, has been reinforced with Epstein-Barr virus colonization and with multiple sclerosis. Early colonization with Epstein-Barr virus protects against multiple sclerosis, late colonization is a risk factor for multiple sclerosis. And then context, the person's immunogenetics meaning do they have more of a tendency to have a very strong pro-inflammatory immune response? And the diversity of the pre-existing colonization. The more diverse your colonization is, it's kind of like one more pathogen in the mix probably won't be a big deal if you have a lot of players because what can happen is you probably can't see this but if there's a lot of bacteria already living in the colony, one more is somewhat policed from running a muck because you have all these other guys that are trying to push them out, if that makes sense, okay? So kind of in summary, if you have late colonization or infection plus poor microbial diversity plus the appropriate genetics, you can have sickness. These microbes that may be good for some may become harmful for you. And that's the real thing I think we're juggling in Westernized societies is that the treponema infection in the HANSA beneficial. If someone here acquired that tomorrow it's probably gonna be pathogenic for you. So we have to be able to kind of separate out what population we're dealing with to know how to treat that person appropriately. Okay, so manipulation of the microbiota. My clinical observations, if diet doesn't fix a problem and I should say diet, lifestyle, maybe some probiotics, maybe some digestive enzymes, if those basics don't fix the problem there is likely a gut infection overgrowth or imbalance at the root of the problem. Okay, now this is from the journal gut in regards to functional bowel disorders. Things that are over to the right here are more effective and higher up here is more invasive. So we wanna be, this is a sweet spot, this is more effective and least invasive. And what do we see? Fottemap diet works pretty well. Probiotics and also gut directed antibiotics but they're a little bit more toward the more invasive end. So what I would submit is a substitute that would maybe fall in this area would be antimicrobial herbs. Herbs that can kill things but don't have quite the same detrimental effect that pharmaceutical antibiotics may have. So diet is powerful and it can influence the microbiota and it can shift the microbiota. The challenge is we don't know enough yet to be able to say you have this condition, we're going to give you this diet to manipulate the microbiota in this way to create this kind of outcome. We don't have that level of data but what we do have is observational studies where people go on this diet with this condition they get better. So some of what we see with the diets preaching the choir here I think but paleo seems to be pretty much good for everything. It's a very good starting point. It's good for general health, weight loss, autoimmunity and digestive conditions. The autoimmune paleo would be a little bit more of a strict application of paleo which usually what I start a patient on in the clinic it will put them on the autoimmune paleo diet we'll see how they do in 30 days later. And for some people, this will completely 100% address their chief complaint in 30 days or so. I'm sure you guys have either had experiences yourself or know people that have. Some specialty diets would be the low FODMAP diet or the SCD diet, which starves bacteria and is best for SIBO and IBS. Ironically, we see so much about how diversity of bacteria is healthy but our clinical interventions tend to be interventions that are geared at killing bacteria and that may have to do with the fact that we have evolved most of us anyway in a very sterile environment. So we may not be able to tolerate this highly diverse bacterial colonization or we may not have a lot of good bacteria to crowd out bad bacteria. So we have this reoccurring problem of bad bacteria continually popping up because we don't have enough good bacteria to crowd them out. And SCD and gaps diet also starves bad bacteria and the gaps provides a lot of good bacteria helpful for SIBO and IBS. SCD may be a little bit better for inflammatory bowel disease as some studies have shown. And then fasting is another intervention that can be useful for people. Remember, we evolved in feeding and fasting or famine and feeding cycles. So fasting is probably somewhat of a normal part of our DNA, if you will. And one of the things that I use clinically is if a patient comes in with a lot of gastrointestinal complaints, we may put them on a three or a four day liquid diet because it's much easier for their system to be able to break that down, break down foods like that. The analogy I use in my patients often is if you sprained your ankle, but you had to run a mile every day, how long would it take your ankle to heal, right? So if it can get you off that ankle, if it can give your gut a break from having to digest these hard food stuff for a few days, that can be really powerful and allowing it to repair itself. So how about weight loss? Well, starting with low carb autoimmune paleo diet is a really good starting point. Then slowly add carbs back into tolerable levels. Because remember, if you're very low carb for too long, if you're consistently under maybe 100 grams, that can cause a loss of healthy bacterial populations and it can cause a decrease in some of the protective short chain fatty acids. So you don't wanna be any more low carb than necessarily have to be. And can I manipulate the microbiota for weight loss? Well, let's look at that. So the microbiota manipulation is an obesity. So we already know that antibiotics used early in life as a risk factor for obesity. And diverse early exposure may be protective. Why is that? Because if you don't have diverse early colonization, you don't get that immune system training and that makes your immune system more prone to inflammation and inflammation can cause things like insulin resistance and impaired metabolism. Low carbohydrate diets show some promising results. 14 pounds loss in a very low carb diet study. A low calorie and low carb study showed 16 pounds lost and a low calorie with low fat showed 13 pounds loss. Now important for me to mention this here, negative changes to the microbiota from very low carbohydrate diets can be offset by supplementation with fiber, prebiotics and resistant starch. They have done studies where they've put obese patients on low carbohydrate diets, but they've given them various prebiotics or resistant starch and they've seen the bacteria populations that normally die flourish. So there's some great implications for if you're someone that really can't tolerate carbohydrate and you have to stay on a long-term low carbohydrate diet, prebiotics and resistant starch may help prevent the loss of short-term fatty acids and other helpful bacteria. Okay, how about fiber? The worst studies regarding fiber show no weight loss. The best results have been with the fiber known as Glucomonin and there was 8.3 more pounds lost than the control group. So two groups, both went on a low calorie diet. One went on a low calorie diet with Glucomonin fiber. That group lost 8.3 pounds more than the control group. So not bad. Other reviews have showed fibers average weight loss. So reviews pool many, many studies. Weight loss would be about 4.2 pounds. So the average loss may be about 4.2. Glucomonin may get you to 8.3 and viscous fibers may be better than non-viscous. So a viscous fiber is one that when you mix it up water forms this kind of thick gel. A non-viscous one is very, very liquid still. Prebiotics, the best studies using prebiotics only show about 2.5 pounds lost. So it doesn't seem like prebiotics can have a massive effect on weight loss. Probiotics, the best results for weight loss here was with lactobacillus remnosus at about 3.7 pounds. Lactobacillus cassari was about 2.2 pounds. So not huge amounts of weight loss that we can achieve with probiotics, prebiotics, but fiber shows some benefit and the one that shows the most benefit is really low carbohydrate diet in this case. Probiotics for Crohn's disease. The best data we have is in maintaining remission with Saccharomyces bilardi and an anti-inflammatory agent or with a probiotic known as VLS3. VLS3 is a blend of different lactobacillus and bifidobacterium species. For all sorts of colitis, there's good evidence for VLS3 alone or with an anti-inflammatory agent and there's very good evidence for E. coli NISL1917. There's a lot of great research on E. coli1917, also known as mutaflora. Unfortunately, it's no longer available in the United States but there were some very impressive studies done with this probiotic. You can still get it. You just have to go through another country. And for maintaining remission and also colitis, the best evidence is for VLS3 or E. coli NISL1917. For IBS, a little different. Bifidobacterium, especially Bifidobacterium infantis, seems to have the best results. And in general, using probiotics that contain soil-based organisms may be an effective way to get closer to dirt. So one of the things that we don't have is enough exposure to dirt. So one of the things that you could do is roll around in the dirt, I guess, or you could take a probiotic that contains some of these soil-based organisms. There's not a ton of clinical trials with these just yet, but I suspect as we see more and more with these, we'll see better and better things. And what I do in the clinic is I usually always use a soil-based probiotic mixed with one of these depending on the condition, with or without prebiotics, depending on the condition also. So kind of my base there. And then the microbiota and autoimmunity. In the functional medicine community, the role of infections in stimulating autoimmunity is an area of great interest at the moment. Aspylori, Epstein-Barr virus, Yersinia enterocolatus, and other infections have shown very strong correlations to autoimmunity, very strong. What we're lacking is a lot of strong data showing if you treat that infection, autoimmunity then goes away. There have been a few studies done. We discussed the one about treating the aspylori infection in patients with Hashimoto's thyroid autoimmunity, and we saw a benefit there. Some of these studies are starting to pop out. They're just kind of slow to be done. But one of the things that I do see routinely is that when we treat infections, it's more often than not, we will see an improvement in autoimmune conditions. And it makes sense if an infection is going to chronically stimulate your immune system and if autoimmunity is just an issue of overzealous immune function, clearing an infection, allowing the immune system to go into relaxation mode, makes sense that it would help in autoimmune condition. The best preventative measures are early and diverse exposure, like we showed with the mothers that had diverse exposure to farm animals while they were pregnant. That's the best, but again, if you're 30 years old and you just came down with an autoimmune condition, you can't really do a whole lot about your upbringing. And a quick word on antimicrobials, which are nature's antibiotic. When pretty much nothing else works, again, look to an infectious issue in the gut. Common infections, SIBO or small intestinal bacterial overgrowth, fungus or candida, worms, amoebas, bacteria and protozoa. And these are things that I find fairly common in patients that have chronic health issues that just won't respond. Natural antimicrobial agents may be as effective as prescriptions in killing what you don't want, but also better at not causing imbalances, which is referenced by this paper here. Natural agents also have additional benefit. Berberine helps lower blood sugar. Artemisia or wormwood is also a very powerful anti-inflammatory. So the nice thing about herbal medicines and the application of getting rid of bad bacteria is they may not kill your good bacteria and they may give you additional health benefit, like anti-inflammatory or increasing your insulin sensitivity. And remember that the immune system and the microbiota have this back and forth and if your immune system is overzealous, it can damage your microbiota. In this meta-analysis, they compared herbals to things like mesalazine and they concluded overall the efficacy and tolerability of herbal medicine in IBD is comparable to five ASA drugs. Again, things like mesalazine. So some of what was used was Artemisia, Boswellia, Andrographis, and Allo as agents that can help dampen this overzealous immune response that some of us have in the United States due to non-diverse exposure during our formative years. So in summary, the microbiota has evolved with humans to allow survival. The microbiota provides important functions in digestion, immunity, metabolism, and detoxification. We should be careful when interpreting microbiota patterns seen in less developed countries. Increased diversity seen is clearly good. Adaptations to higher carbon take is unclear. Early and diverse exposure are key to a healthy microbiota. Getting dirty with old dirt is good for you. The relationship between obesity and the microbiota is unclear other than a decreased diversity is seen in the obese. A manipulation of the microbiota shows promise for modest weight and metabolic improvement and more significant potential for anti-inflammatories and autoimmune conditions using anti-inflammatory agents, antimicrobials, and I should also add probiotics. And finally, diet is a powerful factor that can shift the microbiota. So it was a lot of information. Hopefully you guys learned a few things from it and thank you very much for your time.